Targeted-Microbubble Binding Selectively to GPIIb IIIa Receptors of Platelet Thrombi

Schumann, Patricia A.; Christiansen, J.; Quigley, Rachel M.; McCreery, Thomas P.; Sweitzer, Robert H.; Unger, Evan C.; Lindner, Jonathan R.; Matsunaga, Terry O.

doi:10.1097/00004424-200211000-00001

Cited by 203 publications

(122 citation statements)

References 19 publications

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“…Because of their high echogencity, these targeted agents can be detected by an ultrasound system with high sensitivity, and therefore can provide important information such as the spatial distribution and extent of tumor angiogenesis, 5,6 inflammatory response, 7,8 or thrombus. 9 Current contrast imaging schemes are not yet optimized for imaging these targeted agents because the microbubbles retained in tissue are limited in number, 5,9 and the signal from adherent microbubbles can be masked by the signal from freely circulating microbubbles. Strategies for imaging these agents currently require waiting for clearance of free-floating microbubbles or employing image averaging and subtraction techniques.…”

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confidence: 99%

Asymmetric oscillation of adherent targeted ultrasound contrast agents

Zhao¹,

Ferrara²,

Dayton³

2005

Appl. Phys. Lett.

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With a lipid shell containing biotin, micron-sized bubbles bound to avidin on a porous and flexible cellulose boundary were insonified by ultrasound. The oscillation of these targeted microbubbles was observed by high-speed photography and compared to the oscillation of free-floating microbubbles. Adherent microbubbles were observed to oscillate asymmetrically in the plane normal to the boundary, and nearly symmetrically in the plane parallel to the boundary, with a significantly smaller maximum expansion in each dimension for bound than free bubbles. With sufficient transmitted pressure, a jet was produced traveling toward the boundary.There is a great interest in developing molecularly targeted ultrasound contrast agents due to the potential medical applications. [1][2][3][4] The agents are gas bubbles with a diameter on the order of a few microns and a shell of albumin, lipid, or polymer. After intravenous injection, peptides or antibodies attached to the shells link the agents to a receptor on endothelial cells. Because of their high echogencity, these targeted agents can be detected by an ultrasound system with high sensitivity, and therefore can provide important information such as the spatial distribution and extent of tumor angiogenesis, 5,6 inflammatory response, 7,8 or thrombus. 9 Current contrast imaging schemes are not yet optimized for imaging these targeted agents because the microbubbles retained in tissue are limited in number, 5,9 and the signal from adherent microbubbles can be masked by the signal from freely circulating microbubbles. Strategies for imaging these agents currently require waiting for clearance of free-floating microbubbles or employing image averaging and subtraction techniques. Neither of these techniques is optimal since they require either a time delay, or multiple frames, which impede real-time imaging. Hence, there is a need for the development of a new selective and sensitive method for detecting adherent microbubbles, which will depend on our understanding of the acoustic behavior of a targeted microbubble after it binds to a targeting site.Mathematical simulations have been developed for modeling microbubble radial oscillation with different assumptions and simplifications. [10][11][12] High-speed micrography has been used to study microbubble radial oscillation, 13 translation, 14 and fragmentation. 15 In these studies, a microbubble is assumed to remain spherical and in an infinite medium. Asymmetrical oscillation of a cavitation bubble and formation of a jet have been studied both theoretically and experimentally by a number of research groups, [16][17][18] although previous experimental studies have involved unencapsulated bubbles of a diameter larger than micron-sized contrast agents, and have not used ultrasound as an excitation source. The behavior of a targeted microbubble after it binds to a vessel wall and is insonified by an ultrasound pulse has not been reported previously. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptIn...

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confidence: 99%

Asymmetric oscillation of adherent targeted ultrasound contrast agents

Zhao¹,

Ferrara²,

Dayton³

2005

Appl. Phys. Lett.

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“…The microbubbles loaded with drugs/genes can be targeted to specific (pathologic) sites using different targeting ligands incorporated into bioconjugates (84). Microbubbles are successfully targeted to pathophysiologic processes like inflammation (85), angiogenesis (86), and thrombus formation (87), important in many disease states (eg, atherosclerosis, tumors, transplant rejection, etc.). Although the targeted microbubbles in these applications improve the efficacy of diagnostic imaging, they may also improve US-facilitated drug delivery by increasing the local concentration near the vessel wall.…”

Section: Ultrasound-facilitated Drug Deliverymentioning

confidence: 99%

The role of ultrasound and magnetic resonance in local drug delivery

Deckers

Rome

Moonen

2008

Magnetic Resonance Imaging

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Local drug delivery has recently attracted much attention since it represents a strategy to increase the drug concentration at the target location and decrease systemic toxicity effects. Ultrasound can be used in different ways to trigger regional drug delivery. It can cause the local drug release from a carrier vehicle and the local increase of cell membrane permeability either by a mechanical action or by a temperature increase. Ultrasound contrast agents may enhance these effects by means of cavitation. Ultrasound can be focused deep inside the body into a small region with dimensions on the order of 1 mm. Several types of drug microcarriers have been proposed, from nano-to micrometer sized particles. The objective of real-time imaging of local drug delivery is to assure that the delivery takes place in the target region, that the drug concentration and the resulting physiological reaction are sufficient, and to intervene if necessary. Ultrasound and nuclear imaging techniques play an important role. MRI is rather insensitive but allows precise targeting of (focused) ultrasound, can provide real-time temperature maps, and gives access to a variety of imaging biomarkers that may be used to assess drug action. Examples from recent articles illustrate the potential of the principles of ultrasound-triggered local drug delivery.

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“…It is important to note that contrast agents, whether they are microbubbles or larger-sized nanoparticles, are entirely intravascular agents and they do not leave the vascular compartment (16,17). Therefore to image pathophysiological processes microbubbles are targeted either to disease specific molecules expressed on the endothelial cells, blood cell components (activated leukocytes or platelets) or blood proteins such as fibrin (13,(18)(19)(20)(21)(22)(23). However, nanoparticles, because of their relatively smaller size and longer circulation times, in the regions where vascular permeability is disrupted would leak out and would be able to target extravascular components (24).…”

Section: Targeting Of Contrast Agent For Moelcular Imagingmentioning

confidence: 99%

Cardiovascular Molecular Imaging

2007

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Targeted-Microbubble Binding Selectively to GPIIb IIIa Receptors of Platelet Thrombi

Abstract: The use of receptor selective targeted microbubbles improved binding to vascular thrombi in both in vitro and in vivo settings.

Cited by 203 publications

References 19 publications

Asymmetric oscillation of adherent targeted ultrasound contrast agents

Asymmetric oscillation of adherent targeted ultrasound contrast agents

The role of ultrasound and magnetic resonance in local drug delivery

Cardiovascular Molecular Imaging

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